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Nanog is a promising chemoresistant stemness marker and therapeutic target by iron chelators for esophageal cancer
Author(s) -
Narusaka Toru,
Ohara Toshiaki,
Noma Kazuhiro,
Nishiwaki Noriyuki,
Katsura Yuki,
Kato Takuya,
Sato Hiroaki,
Tomono Yasuko,
Kikuchi Satoru,
Tazawa Hiroshi,
Shirakawa Yasuhiro,
Matsukawa Akihiro,
Fujiwara Toshiyoshi
Publication year - 2021
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33544
Subject(s) - homeobox protein nanog , esophageal cancer , cancer stem cell , cancer research , cancer , medicine , stem cell , cancer cell , oncology , biology , embryonic stem cell , induced pluripotent stem cell , microbiology and biotechnology , biochemistry , gene
Esophageal cancer is a disease showing poor prognosis. Although combination chemotherapy using cisplatin (CDDP) and 5‐fluorouracil is standard for unresectable esophageal cancer, the response rate is 35%. Cancer stem cells (CSCs) and inflammation are reportedly responsible for the poor prognosis of esophageal cancer. However, comprehensive analyses have not been conducted and proposals for progress remain lacking. Iron is known to be a key factor in the stemness of CSCs. Our study focused on the therapeutic potential of iron control using iron chelators for CSCs in esophageal cancer. Among 134 immunohistochemically analyzed cases, Nanog expression was high in 98 cases and low in 36 cases. High Nanog expression correlated with low overall and disease‐free survivals. The iron chelators deferasirox (DFX) and SP10 suppressed the proliferation and expression of stemness markers in TE8 and OE33 cells. DFX and SP10 did not induce compensatory interleukin (IL)‐6 secretion, although CDDP did result in high induction. Moreover, BBI608 and SSZ, as other CSC‐targeting drugs, could not suppress the expression of stemness markers. Overall, Nanog expression appears related to poor prognosis in esophageal cancer patients, and inhibition of stemness and compensatory IL‐6 secretion by iron chelators may offer a novel therapeutic strategy for esophageal cancer.